학술논문
Clinicopathological correlation of cerebrospinal fluid alpha-synuclein seed amplification assay in a behavioral neurology autopsy cohort.
Document Type
Academic Journal
Author
Samudra N; Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.; Fischer DL; Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.; Lenio S; Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.; Lario Lago A; Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.; Ljubenkov PA; Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.; Rojas JC; Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.; Seeley WW; Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.; Spina S; Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.; Staffaroni AM; Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.; Tablante J; Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.; Wekselman F; Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.; Lamoureux J; Amprion Inc., San Diego, California, USA.; Concha-Marambio L; Amprion Inc., San Diego, California, USA.; Grinberg LT; Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.; Department of Pathology, University of California, San Francisco, California, USA.; Boxer AL; Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.; VandeVrede L; Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.
Source
Publisher: John Wiley & Sons, Ltd Country of Publication: United States NLM ID: 101231978 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-5279 (Electronic) Linking ISSN: 15525260 NLM ISO Abbreviation: Alzheimers Dement Subsets: MEDLINE
Subject
Language
English
Abstract
Introduction: Lewy body disease (LBD) is a common primary or co-pathology in neurodegenerative syndromes. An alpha-synuclein seed amplification assay (αSyn-SAA) is clinically available, but clinical performance, especially lower sensitivity in amygdala-predominant cases, is not well understood.
Methods: Antemortem CSF from neuropathology-confirmed LBD cases was tested with αSyn-SAA (N = 56). Diagnostic performance and clinicopathological correlations were examined.
Results: Similar to prior reports, sensitivity was 100% for diffuse and transitional LBD (9/9), and overall specificity was 96.3% (26/27). Sensitivity was lower in amygdala-predominant (6/14, 42.8%) and brainstem-predominant LBD (1/6, 16.7%), but early spread outside these regions (without meeting criteria for higher stage) was more common in αSyn-SAA-positive cases (6/7, 85.7%) than negative (2/13, 15.4%).
Discussion: In this behavioral neurology cohort, αSyn-SAA had excellent diagnostic performance for cortical LBD. In amygdala- and brainstem-predominant cases, sensitivity was lower, but positivity was associated with anatomical spread, suggesting αSyn-SAA detects early LBD progression in these cohorts.
Highlights: A cerebrospinal fluid alpha-synuclein assay detects cortical LBD with high sensitivity/specificity. Positivity in prodromal stages of LBD was associated with early cortical spread. The assay provides precision diagnosis of LBD that could support clinical trials. The assay can also identify LBD co-pathology, which may impact treatment responses.
(© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Methods: Antemortem CSF from neuropathology-confirmed LBD cases was tested with αSyn-SAA (N = 56). Diagnostic performance and clinicopathological correlations were examined.
Results: Similar to prior reports, sensitivity was 100% for diffuse and transitional LBD (9/9), and overall specificity was 96.3% (26/27). Sensitivity was lower in amygdala-predominant (6/14, 42.8%) and brainstem-predominant LBD (1/6, 16.7%), but early spread outside these regions (without meeting criteria for higher stage) was more common in αSyn-SAA-positive cases (6/7, 85.7%) than negative (2/13, 15.4%).
Discussion: In this behavioral neurology cohort, αSyn-SAA had excellent diagnostic performance for cortical LBD. In amygdala- and brainstem-predominant cases, sensitivity was lower, but positivity was associated with anatomical spread, suggesting αSyn-SAA detects early LBD progression in these cohorts.
Highlights: A cerebrospinal fluid alpha-synuclein assay detects cortical LBD with high sensitivity/specificity. Positivity in prodromal stages of LBD was associated with early cortical spread. The assay provides precision diagnosis of LBD that could support clinical trials. The assay can also identify LBD co-pathology, which may impact treatment responses.
(© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)